Abstract
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P <5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P <5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
| Original language | English |
|---|---|
| Article number | ddq307 |
| Pages (from-to) | 4072-4082 |
| Number of pages | 11 |
| Journal | Human Molecular Genetics |
| Volume | 19 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - Jul 27 2010 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
- Molecular Biology
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A genome-wide scan for common alleles affecting risk for autism. / Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J.; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim.
In: Human Molecular Genetics, Vol. 19, No. 20, ddq307, 27.07.2010, p. 4072-4082.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A genome-wide scan for common alleles affecting risk for autism
AU - Anney, Richard
AU - Klei, Lambertus
AU - Pinto, Dalila
AU - Regan, Regina
AU - Conroy, Judith
AU - Magalhaes, Tiago R.
AU - Correia, Catarina
AU - Abrahams, Brett S.
AU - Sykes, Nuala
AU - Pagnamenta, Alistair T.
AU - Almeida, Joana
AU - Bacchelli, Elena
AU - Bailey, Anthony J.
AU - Baird, Gillian
AU - Battaglia, Agatino
AU - Berney, Tom
AU - Bolshakova, Nadia
AU - Bölte, Sven
AU - Bolton, Patrick F.
AU - Bourgeron, Thomas
AU - Brennan, Sean
AU - Brian, Jessica
AU - Carson, Andrew R.
AU - Casallo, Guillermo
AU - Casey, Jillian
AU - Chu, Su H.
AU - Cochrane, Lynne
AU - Corsello, Christina
AU - Crawford, Emily L.
AU - Crossett, Andrew
AU - Dawson, Geraldine
AU - de Jonge, Maretha
AU - Delorme, Richard
AU - Drmic, Irene
AU - Duketis, Eftichia
AU - Duque, Frederico
AU - Estes, Annette
AU - Farrar, Penny
AU - Fernandez, Bridget A.
AU - Folstein, Susan E.
AU - Fombonne, Eric
AU - Freitag, Christine M.
AU - Gilbert, John
AU - Gillberg, Christopher
AU - Glessner, Joseph T.
AU - Goldberg, Jeremy
AU - Green, Jonathan
AU - Guter, Stephen J.
AU - Hakonarson, Hakon
AU - Heron, Elizabeth A.
AU - Hill, Matthew
AU - Holt, Richard
AU - Howe, Jennifer L.
AU - Hughes, Gillian
AU - Hus, Vanessa
AU - Igliozzi, Roberta
AU - Kim, Cecilia
AU - Klauck, Sabine M.
AU - Kolevzon, Alexander
AU - Korvatska, Olena
AU - Kustanovich, Vlad
AU - Lajonchere, Clara M.
AU - Lamb, Janine A.
AU - Laskawiec, Magdalena
AU - Leboyer, Marion
AU - Le Couteur, Ann
AU - Leventhal, Bennett L.
AU - Lionel, Anath C.
AU - Liu, Xiao Qing
AU - Lord, Catherine
AU - Lotspeich, Linda
AU - Lund, Sabata C.
AU - Maestrini, Elena
AU - Mahoney, William
AU - Mantoulan, Carine
AU - Marshall, Christian R.
AU - McConachie, Helen
AU - McDougle, Christopher J.
AU - McGrath, Jane
AU - McMahon, William M.
AU - Melhem, Nadine M.
AU - Merikangas, Alison
AU - Migita, Ohsuke
AU - Minshew, Nancy J.
AU - Mirza, Ghazala K.
AU - Munson, Jeff
AU - Nelson, Stanley F.
AU - Noakes, Carolyn
AU - Noor, Abdul
AU - Nygren, Gudrun
AU - Oliveira, Guiomar
AU - Papanikolaou, Katerina
AU - Parr, Jeremy R.
AU - Parrini, Barbara
AU - Paton, Tara
AU - Pickles, Andrew
AU - Piven, Joseph
AU - Posey, David J.
AU - Poustka, Annemarie
AU - Poustka, Fritz
AU - Prasad, Aparna
AU - Ragoussis, Jiannis
AU - Renshaw, Katy
AU - Rickaby, Jessica
AU - Roberts, Wendy
AU - Roeder, Kathryn
AU - Roge, Bernadette
AU - Rutter, Michael L.
AU - Bierut, Laura J.
AU - Rice, John P.
AU - Salt, Jeff
AU - Sansom, Katherine
AU - Sato, Daisuke
AU - Segurado, Ricardo
AU - Senman, Lili
AU - Shah, Naisha
AU - Sheffield, Val C.
AU - Soorya, Latha
AU - Sousa, Inês
AU - Stoppioni, Vera
AU - Strawbridge, Christina
AU - Tancredi, Raffaella
AU - Tansey, Katherine
AU - Thiruvahindrapduram, Bhooma
AU - Thompson, Ann P.
AU - Thomson, Susanne
AU - Tryfon, Ana
AU - Tsiantis, John
AU - van Engeland, Herman
AU - Vincent, John B.
AU - Volkmar, Fred
AU - Wallace, Simon
AU - Wang, Kai
AU - Wang, Zhouzhi
AU - Wassink, Thomas H.
AU - Wing, Kirsty
AU - Wittemeyer, Kerstin
AU - Wood, Shawn
AU - Yaspan, Brian L.
AU - Zurawiecki, Danielle
AU - Zwaigenbaum, Lonnie
AU - Betancur, Catalina
AU - Buxbaum, Joseph D.
AU - Cantor, Rita M.
AU - Cook, Edwin H.
AU - Coon, Hilary
AU - Cuccaro, Michael L.
AU - Gallagher, Louise
AU - Geschwind, Daniel H.
AU - Gill, Michael
AU - Haines, Jonathan L.
AU - Miller, Judith
AU - Monaco, Anthony P.
AU - Nurnberger, John I.
AU - Paterson, Andrew D.
AU - Pericak-Vance, Margaret A.
AU - Schellenberg, Gerard D.
AU - Scherer, Stephen W.
AU - Sutcliffe, James S.
AU - Szatmari, Peter
AU - Vicente, Astrid M.
AU - Vieland, Veronica J.
AU - Wijsman, Ellen M.
AU - Devlin, Bernie
AU - Ennis, Sean
AU - Hallmayer, Joachim
PY - 2010/7/27
Y1 - 2010/7/27
N2 - Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P <5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P <5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
AB - Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P <5 3 10-28. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P <5 × 10-28 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
UR - http://www.scopus.com/inward/record.url?scp=77957735529&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957735529&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddq307
DO - 10.1093/hmg/ddq307
M3 - Article
C2 - 20663923
AN - SCOPUS:77957735529
VL - 19
SP - 4072
EP - 4082
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 20
M1 - ddq307
ER -